Traditional Chinese Medicine treatment as maintenance therapy in advanced non-small-cell lung cancer: A randomized controlled trial

ObjectivesMaintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) is an increasingly hot topic in the field of clinical NSCLC research. This study aimed to evaluate the effects of Traditional Chinese Medicine (TCM) treatment as maintenance therapy on time to progression (TTP), quality of life (QOL), overall survival (OS) and 1-year survival rate in patients with advanced NSCLC.MethodsThis study was conducted as a randomized, controlled, open-label trial. 64 non-progressive patients who responded to initial therapy were randomized 1:1 to the TCM arm (treated with herbal injection (Cinobufacini, 20 ml/d, d1–d10), herbal decoction (d1–d21) and Chinese acupoint application (d1–d21), n = 32) or to the chemotherapy arm (treated with pemetrexed (non-squamous NSCLC, 500 mg/m², d1), docetaxel (75 mg/m², d1) or gemcitabine (1250 mg/m², d1 and d8), n = 32). Each therapy cycle was 21 days. They were repeated until disease progression, unacceptable toxicity, or until the patients requested therapy discontinuation. The primary end point was TTP; the secondary end points were QOL, OS and 1-year survival rate. “Intention-to-treat” analysis included all randomized participants.ResultsTCM treatment prolonged median TTP for 0.7 months compared with chemotherapy, but it was not statistically significant (3.0 months vs. 2.3 months, P = 0.114). Median OS time for TCM treatment did not offer a significant advantage over for chemotherapy (21.5 months vs. 18.8 months, P = 0.601). 1-year survival rate of TCM treatment significantly improved than that of chemotherapy (78.1% vs. 53.1%, P = 0.035). TCM treatment can significantly improve QOL when compared to chemotherapy as assessed by EORTC QLQ-C30 and EORTC QLQ-LC13 QOL instruments.ConclusionsTCM maintenance treatment had similar effects on TTP and OS compared with maintenance chemotherapy, but it improved patients' QOL and had higher 1-year survival rate. TCM Maintenance treatment is a promising option for advanced NSCLC patients without progression following first-line chemotherapy.     

Serum neural precursor cell-expressed,developmentally down regulated 9 (NEDD9) level may have a prognostic role in patients with gastric cancer

BackgroundNeural precursor cell-expressed, developmentally down regulated 9 (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved in cancer cell adhesion, migration and invasion. The prognostic value of NEDD9 has been evaluated before and its expression is a predictor of poor prognosis in cancer patients. The objective of this study was to determine the clinical significance of the serum levels of NEDD9 in gastric cancer (GC) patients.Patients and methodsA total of 68 patients with a pathologically confirmed diagnosis of GC were enrolled into this study. Serum NEDD9 concentrations were determined by the solid-phase sandwich (ELISA) method. Twenty-eight healthy age- and sex-matched controls were included into the analysis.ResultsThe median age at diagnosis was 60 years, range 21 to 84 years. Forty-nine (72%) patients were male and cardia was the most common tumor localization (n = 37, 77%) in GC patients. The most frequent histologic subtype was adenocarcinoma (n = 45, 66%). Liver was the most common metastatic site in 32 patients with metastasis (n = 14, 44%). Sixty-one percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. The median follow-up time was 8 months (range 1 to 23 months). At the end of the observation period, 17 patients (25%) experienced disease progression and 28 of the remaining patients (41%) died. Median progression-free survival (PFS) and overall survival (OS) of the whole group were 4.0 ± 0.7 months [95% confidence interval (CI) = 3–5 months] and 14.6 ± 1.2 months (95% CI = 12–17 months), respectively. One-year and 2-year OS rates were 54.4% (95% CI = 41.3–67.5) and 51.2% (95% CI = 37.3–65.1), respectively. The median serum NEDD9 levels of GC patients were significantly higher than controls (1339.51 vs. 1187.91 pg/mL, P = 0.02). There was no significant difference according to known disease-related clinicopathological or laboratory parameters (P > 0.05). Serum NEDD9 levels had a significant impact on PFS (P = 0.04). On the other hand, serum NEDD9 levels showed no significantly adverse effect on OS (P = 0.50).ConclusionSerum NEDD9 level may be a diagnostic marker for GC patients. Moreover, our study results showed that it was elevated in GC patients and had an unfavorable prognostic effect. However, it has no predictive role on CTx response.     

Decreased expression of microRNA-148a predicts poor prognosis in ovarian cancer and associates with tumor growth and metastasis

ObjectiveMicroRNA-148a (MiR-148a) had been reported to take part in some cancer progresses, but its clinical significance in ovarian cancer had been rarely reported. The purpose of this study was to evaluate the prognostic value of miR-148a as well as its roles in ovarian cancer progression.MethodsRelative expression of miR-148a in the plasma specimens of ovarian cancer patients was detected by qRT-PCR. Chi-square test was used to analyze the relationship between miR-148a expression and clinical characteristics. The overall survival was analyzed by Kaplan-Meier method and Cox regression analysis was used to evaluate the prognostic value of miR-148a. In addition, the ovarian cancer cell line SKOV-3 was separately transfected with pcDNA3-microRNA-148a over-expression vector and pcDNA3 empty vector to detect the functional roles of miR-148a in ovarian cancer progression.ResultsDecreased level of plasma miR-148a was observed in ovarian cancer patients compared with healthy controls. The expression level was associated with histopathologic grade, TNM stage and lymph node metastasis (P < 0.05 for all). Besides, patients with high level of miR-148a had a longer survival time than those with low level (40.3 months vs 31.6 months, log rank test, P = 0.002). Cox regression analysis indicated that miR-148a might be a potential biomarker for ovarian cancer prognosis (HR = 1.699, 95%CI = 1.175-2.456, P = 0.005). Moreover, cell experiments confirmed that miR-148a could inhibit proliferation, migration and invasion of ovarian cancer cells.ConclusionMiR-148a may be a potential prognostic factor for ovarian cancer and it can suppress tumor progression.     

Associations Among Hypogonadism,C-Reactive Protein,Symptom Burden,and Survival in Male Cancer Patients with Cachexia: A Preliminary Report

ContextCachexia is characterized by muscle wasting, anorexia, and elevated inflammatory markers. In patients without cancer, hypogonadism is associated with lower lean body mass, increased symptom burden, and decreased survival. Hypogonadism in cancer cachexia could exacerbate symptoms, facilitate a proinflammatory state, and decrease survival.ObjectivesTo explore the relationships among these factors, a retrospective study of male cancer patients was conducted.MethodsThe charts of 98 consecutive male patients referred to a cachexia clinic at a comprehensive cancer center were reviewed. All patients reported weight loss of >5% within the preceding six months; the median age was 60 years. Fifty-seven (58%) had serum C-reactive protein (CRP), and 68 (69%) had total testosterone evaluated. Symptoms were evaluated by the Edmonton Symptom Assessment Scale.ResultsMedian CRP was 20 mg/L, and median testosterone level was 185 ng/dL (6.42 nmol/L) (normal ≥240 ng/dL or 8.36 nmol/L). There was an inverse correlation between testosterone and CRP levels (P < 0.01). Lower testosterone was associated with increased dyspnea and insomnia (P < 0.05). Poor appetite and insomnia (P < 0.05) correlated with elevated CRP. Survival of patients with testosterone levels ≤185 ng/dL (6.42 nmol/L) was decreased compared with that of those with levels >185 ng/dL (13 vs. 62 weeks, P = 0.004). Patients with CRP levels >10 mg/L had decreased survival compared with those with levels ≤10 mg/L (15 vs. 46 weeks, P = 0.01). The combination of hypogonadism and elevated CRP was associated with poorer prognosis. Elevated CRP levels were associated with increased symptom burden and decreased survival. Low testosterone was associated with decreased survival and correlated inversely with CRP levels, dyspnea, and insomnia.ConclusionOur preliminary results suggest that testosterone and CRP may be additive or synergistic as markers for survival in male patients and could be useful in future prognostic models.     

Diagnostic and prognostic potentials of microRNA-27a in osteosarcoma

AimGrowing evidence suggest that the microRNA (miR)-23a/24-2/27a cluster may play a crucial role in mammary tumorigenesis and act as a novel class of oncogenes. Among these members, miR-27a has been reported to promote proliferation, migration and invasion in human osteosarcoma cells. The aim of this study was to detect the serum levels of miR-27a in osteosarcoma patients and to investigate its associations with clinicopathological features and prognosis.MethodsmiR-27a levels in sera from 166 osteosarcoma patients and 60 healthy controls were detected by real-time quantitative RT-PCR. Then, the associations of serum miR-27a level with clinicopathological factors or survival of osteosarcoma patients were further evaluated.ResultsCompared to healthy controls, the serum levels of miR-27a were significantly increased in osteosarcoma patients (P < 0.001). Importantly, miR-27a could efficiently screen osteosarcoma patients from healthy controls (Area under receiver operating characteristic curve, AUC = 0.867). Then, high miR-27a expression was more frequently occurred in osteosarcoma patients with advanced clinical stage (P = 0.001), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.008). In Kaplan–Meier survival analysis, high miR-27a expression was a significant indicator for poor overall survival (P = 0.006) as well as poor disease-free survival (P = 0.01). Furthermore, multivariate analysis demonstrated that miR-27a expression was an independent and significant prognostic factor to predict overall survival (P = 0.01) and disease-free survival (P = 0.03).ConclusionmiR-27a expression may be elevated in sera of osteosarcoma patients and in turn contributes to aggressive progression of this malignancy. Detection of serum miR-27a levels may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.     

Protein regulator of cytokinesis 1 overexpression predicts biochemical recurrence in men with prostate cancer

BackgroundProtein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer-specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy.Materials and methodsPRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed.ResultsPRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P < 0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P < 0.001).ConclusionThese findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy.     

Chinese herbal medicine as maintenance therapy for improving the quality of life for advanced non-small cell lung cancer patients

ObjectiveThe purpose of the study was to assess the efficacy and safety of using Chinese herbal medicine (CHM) as maintenance therapy considering the survival of advanced non-small-cell lung cancer (NSCLC) patients after first-line conventional platinum-based chemotherapy.DesignAn open-label, randomized, controlled trial.SettingFour hospitals in China.Interventions and main outcome measuresA total of 106 patients were eligible and randomly divided into two groups from four hospitals in China. Both groups received the best supporting care (BSC). Additionally, patients in the trial group were given CHM every day until the disease became aggravated or the patients resigned. The study took both progression-free survival (PFS) and quality of life (QOL) as the primary outcomes to comprehensively evaluate the effect of the treatment. QOL was measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) 4.0 questionnaire. Side effects and safety were evaluated at the same time.ResultsOf the 106 patients, 99 completed the study. After treatment and follow-up for PFS, there were no significant differences in the median PFS time and the 6-month PFS probability between the two groups. However, the 3-month PFS probability in the trial group was significantly higher than that in the control group (FAS, PPS: P < 0.01). For QOL, there were significant differences between the two groups in the following: physical well-being, emotional well-being, functional well-being, lung cancer symptom domain and total score of the FACT-L4.0 (FAS, PPS: P < 0.05). There was no significant difference in the social well-being domain. No serious adverse side effects to the treatment were observed.ConclusionsCHM is well tolerated and may improve the QOL of advanced NSCLC patients. CHM is worth studying in future investigations.     

The prognostic value of serum pregnancy-associated plasma protein A,S100 and high sensitivity C-reactive protein in acute ischemic stroke patients without heparin administration

ObjectivesThe concerns regarding the pre-analytical bias caused by medicine treatments have been raised in the diagnosis and prognosis of ischemic stroke recently. The aim of this study was to examine the prognostic value of serum pregnancy-associated plasma protein A (PAPP-A), S100 and high sensitivity C-reactive protein (hs-CRP) in heparin-naïve patients of acute ischemic stroke.Design and methodsSerum levels of PAPP-A, S100 and hs-CRP were determined in 205 heparin-naïve patients of acute ischemic stroke and 50 healthy controls. Clinical information and radiological information were collected. Unfavorable outcomes (stroke recurrence, myocardial infarction or death) were also recorded after six months. The associations between serum biomarker levels and stroke severity/outcome were assessed.ResultsSerum PAPP-A, S100 and hs-CRP levels increased in patients compared with controls (P < 0.05). S100 and hs-CRP levels were significantly higher in patients with larger cerebral infarction sizes (P < 0.05) and more severe neurological impairment (P < 0.05). Serum PAPP-A level showed a progressive increase with the increase of stroke severity (P < 0.05). Serum hs-CRP and National Institutes of Health Stroke Scale (NIHSS) scores were identified as independent predictors for unfavorable outcomes with odds ratios of 2.884 (1.154 to 7.210, P = 0.023) and 2.887 (1.146 to 7.273, P = 0.024), respectively.ConclusionSerum PAPP-A, S100 and hs-CRP were associated with stroke severity or outcome after ischemic stroke and may offer complementary information, essential for clinical decision making. Serum PAPP-A showed a potential value for the evaluation of stroke clinically.     

Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers?

Cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors. The purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule-1 (ALCAM) and intercellular adhesion molecule-1 (ICAM-1) in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). The median age at diagnosis was 59.5 years (range 32–82 years). Tumor localizations of the majority of the patients were antrum (n = 42, 72.4%) and tumor histopathologies of the majority of the patients were diffuse (n = 43, 74.1%). The majority of the patients had stage IV disease (n = 41, 70.7%). Thirty six (62.1%) patients had lymph node involvement. The median follow-up time was 66 months (range 1–97.2 months). At the end of the observation period, 26 patients (44.8%) were dead. The median survival for all patients was 21.4 ± 5 months (%95 CI, 11.5–31.3). The 1-year survival rates were 66.2%.The baseline serum ALCAM levels of the patients were significantly higher than those of the controls (p = 0.001). There was no significant difference in the serum levels of ICAM-1 between the patients and controls (p = 0.232). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Tumor localization (p = 0.03), histopathology (p = 0.05), and response to chemotherapy (p = 0.003) had prognostic factors on survival. Neither serum ALCAM levels nor serum ICAM-1 levels were identified to have a prognostic role on overall survival (ICAM-1 p = 0.6, ALCAM p = 0.25). In conclusion, serum levels of ALCAM were found to have diagnostic value in GC patients.     

Inter-alpha-trypsin inhibitor heavy chain H4 as a diagnostic and prognostic indicator in patients with hepatitis B virus-associated hepatocellular carcinoma

ObjectivesInter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with various diseases. We evaluated the diagnostic and prognostic significance of serum ITIH4 levels in healthy controls and patients with chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC).Design and methodsThe study enrolled 300 individuals (50 healthy controls, 50 with CHB, 100 with HBV-associated cirrhosis, and 100 with HBV-associated HCC). Serum ITIH4 levels were determined by western blot analysis and expressed in densitometry units (DU).ResultsITIH4 levels were higher in CHB (mean: 252.96 DU) and liver cirrhosis (mean: 206.43 DU) patients than in healthy controls (mean: 75.92 DU) and HCC patients (mean: 92.86 DU) (P < 0.001). The area under the receiver operating characteristic curve was 0.71 for the diagnosis of HCC in patients with HBV-related liver disease. Multivariate Cox regression analysis showed that large tumor size (≥ 5 cm) was independently associated with overall survival (hazard ratio 5.894, 95% confidence interval 1.373–25.300, P = 0.017). A Kaplan–Meier survival analysis showed significantly worse survival among HCC patients with both low ITIH4 (< 80 DU) and a large tumor size compared to that among other HCC patients (P < 0.001), and among patients with high AFP (> 200 ng/mL) and low ITIH4 compared to that among other HCC patients (P = 0.041).ConclusionsSerum ITIH4 levels are reduced in HCC patients compared to that in CHB and cirrhosis patients, and low serum ITIH4 levels are associated with shorter survival in HBV-associated HCC patients.     

BCL2L12: A promising molecular prognostic biomarker in breast cancer

ObjectivesBCL2-like 12 (BCL2L12) is a new member of the BCL2 gene family that was discovered and cloned by members of our group and found to be expressed in the mammary gland. Many genes of the BCL2 family were found to be implicated in breast carcinogenesis and to serve as possible prognostic markers. The aim of the present study was the quantification of BCL2L12 mRNA expression in order to assess its value as a prognostic tissue biomarker in breast cancer (BC).Design and methodsBCL2L12 mRNA levels were determined in a statistically significant sample size of cancerous (N = 108) and adjacent non-cancerous (N = 71) breast tissues using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Relative quantification analysis was conducted using the comparative C_T (2^− ΔΔC_T) method, whereas the association between BCL2L12 expression and clinopathological data, disease-free survival (DFS) and overall survival (OS) were estimated by statistical analysis.ResultsBCL2L12 mRNA expression was decreased in malignant samples compared to the histologically normal counterparts (p = 0.012). Significant relationships between BCL2L12 expression and TNM stages (p = 0.009), metastatic potential (p = 0.012), tumor size (p = 0.04) and age (p = 0.024) were observed. Moreover, Kaplan–Meier and Cox univariate analyses indicated that BCL2L12 expression is associated with longer DFS, whereas multivariate analysis pointed out the independent favorable prognostic value of BCL2L12.ConclusionsAccording to our results, BCL2L12 mRNA expression is a favorable prognostic marker of DFS for BC patients, suggesting its possible application as a novel prognostic indicator of this malignancy.     

Evaluation of serum soluble OX40 ligand as a prognostic indicator in acute coronary syndrome patients

BackgroundLong-term risk stratification in patients presented with acute coronary syndromes (ACS) is possible by measuring cardiac troponin (cTn). The present study evaluates the clinical predictive value of increased serum soluble OX40 ligand (sOX40L) in patients with ACS and acute chest pain.MethodsThe levels of serum soluble OX40L were measured by ELISA in patients with ACS (168) and acute chest pain (106). The platelet activation was assessed by flow cytometry.ResultsThe levels of serum soluble OX40L were increased (> 40.0 ng/ml) in 56 patients with ACS (33.3%) and in 17 patients with acute chest pain (> 40.0 ng/ml), respectively. The increased sOX40L level was significantly correlated with measured levels of troponin I (r = 0.47, p < 0.001) and the increased soluble OX40L levels (> 40.0 ng/ml) were associated with higher risk for acute myocardial infarction (AMI), sudden death and recurrent angina. Both increased serum levels of sOX40L and cTnT showed a significantly increased risk of major adverse cardiovascular events (including AMI, sudden death and recurrent angina) in two groups during 30 days, 6 months and 9 months of follow-up.ConclusionIn patients with ACS, elevation of baseline sOX40L levels indicates an increased risk for cardiovascular events. Serum soluble OX40L might be a useful prognostic marker or indicator for adverse events in patients with ACS.     

Plasma and synovial fluid sclerostin are inversely associated with radiographic severity of knee osteoarthritis

ObjectiveThe purpose of this study was to analyze sclerostin in plasma and synovial fluid of knee osteoarthritis (OA) patients and to investigate the association between sclerostin levels and radiographic severity.Design and methodsA total of 190 subjects (95 knee OA patients and 95 healthy controls) were recruited in the present study. Sclerostin levels in plasma and synovial fluid were assessed using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren–Lawrence classification.ResultsPlasma sclerostin levels were significantly lower in OA patients than in healthy controls (P = 0.004). Additionally, sclerostin levels in plasma were significantly higher with respect to paired synovial fluid (P < 0.001). Moreover, sclerostin levels in plasma and synovial fluid demonstrated a significant inverse correlation with the radiographic severity of knee OA (r = − 0.464, P < 0.001 and r = − 0.592, P < 0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and synovial sclerostin levels (r = 0.657, P < 0.001).ConclusionsSclerostin was significantly lower in OA plasma samples when compared with healthy controls. Plasma and synovial fluid sclerostin levels were inversely associated with the radiographic severity of knee OA. Therefore, sclerostin may be utilized as a biochemical marker for reflecting disease severity in primary knee OA.     

Circulating fetuin-A predicts early mortality in chronic hemodialysis patients

ObjectivesThe purpose of this study was to assess whether low serum levels of fetuin-A are potential biochemical predictor of early and/or late survival in chronic hemodialysis (HD) patients.Design and methodsWe measured serum levels of fetuin-A in 67 patients on chronic HD, and correlated it to 3, 12, and 24 months mortality.ResultsCumulative death rate was 7%, 19%, and 37% deaths at 3, 12, and 24 months. Serum fetuin-A was significantly lower in 3 months and 12 months non-survivals (p < 0.001), but not in 24 months non-survivals. Kaplan–Meier analyses based on fetuin-A tertiles showed statistically significantly increased probability of death up to 12 months of follow-up for decreasing fetuin-A concentrations (p < 0.008).ConclusionsFetuin-A as a circulating inhibitor of vascular calcification was significant predictor of early mortality in chronic HD patients but did not appear as a fair marker for later survival.     

Soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid is inversely associated with disease severity of knee osteoarthritis

Objectives:The aim of this study was to measure soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid of knee osteoarthritis (OA) patients and to determine the correlation between sRAGE levels and disease severity.Design and methods:Thirty-six OA patients and 15 healthy controls were enrolled in this study. OA grading was performed using the Kellgren–Lawrence classification. sRAGE levels in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay.Results:Plasma sRAGE levels were significantly lower in OA patients than in healthy controls (P = 0.01). sRAGE levels in plasma were remarkably higher with regard to paired synovial fluid (P = 0.001). Additionally, sRAGE concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity (r = ?0.65, P < 0.001 and r = ?0.55, P = 0.001, respectively). Further analysis showed that there was a strong positive correlation between plasma and synovial sRAGE concentration (r = 0.81, P < 0.001).Conclusions:sRAGE levels were significantly lower in OA patients compared with controls, and sRAGE levels in plasma and synovial fluid also decreased significantly as the disease severity increased. Accordingly, sRAGE levels could be used as a biochemical marker for assessing the severity and progression of knee OA.     

Expression of STK15 mRNA in hepatocellular carcinoma and its prognostic significance

ObjectivesTo investigate whether the STK15 mRNA expression correlates with clinicopathologic features and the prognosis of HCC patients.Design and methodsThree hepatoma cell lines, two normal liver epithelial cell lines, hepatoma tissues, adjacent tumor tissues and normal liver tissues were obtained from 46 HCC patients. Semi-quantitative RT-PCR assays were performed to detect the expression of STK15 mRNA in above cell lines and tissues. Moreover, the expression of STK15 protein in hepatoma tissues, adjacent tumor tissues and normal liver tissues was also examined by immunohistochemical staining. Finally, correlations between STK15 mRNA expression and the clinicopathological features and prognosis of HCC patients were evaluated.ResultsSTK15 mRNA showed higher levels in hepatoma cell lines than in normal liver epithelial cell lines. Moreover, the mean levels of STK15 mRNA and protein expression showed statistical difference between tumor tissues, tumor adjacent tissues and normal liver tissues (P < 0.01). By immunohistochemical analysis, we found that paraffin-embedded archival HCC tissues showed higher expression of STK15 than adjacent tumors and normal liver tissues. Furthermore, HCC patients with higher STK15 mRNA expression showed poorer prognosis than those with lower STK15 mRNA expression. The high level of STK15 mRNA expression was significantly correlated with tumor stage (P = 0.0081), more frequent lymph node (P = 0.0380) or hematogenous metastasis (P = 0.0066), and a higher incidence of cancer-related death (P = 0.0083). Furthermore, the disease-free survival (DFS) and overall survival (OS) rates of HCC patients with higher STK15 mRNA expression group (47.6% and 52.7%) were significantly lower than those of patients with low STK15 mRNA expression group (56.9% and 68.8%, P = 0.0018 and 0.0047).ConclusionsSTK15 mRNA might be a good marker for predicting the prognosis of HCC patients.     

Effects of anticoagulants on human plasma soluble corin levels measured by ELISA

BackgroundRecently, soluble corin was detected in human plasma. In patients with heart failure, plasma corin levels were lower than that of normal controls. In this study, we analyzed experimental conditions for measuring plasma or serum corin by an immunoassay.MethodsSerum and plasma corin levels were measured by ELISA. Effects of different anticoagulants (EDTA, heparin and sodium citrate) on plasma corin levels were examined.ResultsCorin levels in serum were similar to that in plasma with heparin (950 ± 305 vs. 929 ± 301 pg/ml, n = 40, p = 0.73), but were significantly higher than those in plasma with sodium citrate (735 ± 237 pg/ml, p < 0.01) or EDTA (716 ± 261 pg/ml, p < 0.001). Native and recombinant human corin proteins were stable in human plasma with EDTA at 4 °C or underwent freezing-and-thawing. In 348 healthy Chinese individuals, plasma corin levels ranged from 216 to 1663 pg/ml. The levels were higher in males than that in females (842 ± 283 vs. 569 ± 192 pg/ml, p < 0.001).ConclusionSoluble corin was stable in plasma samples. Plasma soluble corin levels vary depending on anticoagulants used. Samples containing heparin had significantly higher levels of corin than that in samples with EDTA or sodium citrate.     

Up-regulated microRNA-155 expression is associated with poor prognosis in cervical cancer patients

BackgroundMicroRNAs (miRNAs) play important roles in tumor development and progression. The purposes of the study was to investigate the role of miR-155 in cervical cancer.MethodsQuantitative real-time RT-PCR (qRT-PCR) was performed to examine miR-155 expression in cervical cancer tissues and adjacent non-cancerous tissues. The association with overall survival of patients was analyzed by Kaplan-Meier survival analysis. Small interfering RNA (siRNA) was used to suppress miR-155 expression in cervical cancer cells. In vitro assays were performed to further explore the biological functions of miR-155 in cervical cancer.ResultsWe found that miR-155 expression was markedly up-regulated in cervical cancer tissues and correlated with FIGO stage, lymph nodes metastasis, vascular invasion and HPV. Patients with high miR-155 expression level had poorer overall survival than those with low miR-155 expression. Furthermore, multivariate Cox regression analysis suggested that increased miR-155 was an independent prognostic indicator for cervical cancer (P = 0.007; HR = 2.320; 95%CI: 1.259–4.276). Moreover, knockdown of miR-155 was demonstrated to inhibit cell proliferation, migration, and invasion in vitro.ConclusionOur study presents that miR-155 is a novel molecule involved in cervical cancer progression, which provide a potential prognostic biomarker and therapeutic target.